Total Synthesis of Ningalin C

Full text of DOI:10.1002/bkcs.11609

Note
DOI: 10.1002/bkcs.11609
BULLETIN OF THE
W.-H. Kim et al.
KOREAN CHEMICAL SOCIETY
Total Synthesis of Ningalin C
*
Woo-Hyung Kim, Jang-Yeop Kim, and Cheon-Gyu Cho
Department of Chemistry, Center for New Directions in Organic Synthesis, Hanyang University, Seoul
04763, South Korea. *E-mail: ccho@hanyang.ac.kr
Received September 4, 2018, Accepted September 18, 2018
Keywords: Aryl hydrazide, Total synthesis, Ningalin C, Indolization, C N coupling
Ningalin C is a highly colored pyrrole alkaloid isolated
from an unidentified Western Australian ascidian of the
genus Didemnum by Fenical et al., together with biogeneti-
cally related congeners, ningalins A, B, and D, all of which
are derived from 3,4-dihydroxyphenylalanine in biosyn-
thetic pathway.1 Structurally, it is composed of a densely
substituted benzo[e]indole-2,5(3H)-dione core, two o-
catechol subunits and 3,4-dihydroxyphenethyl chain on the
pyrrole nitrogen (Figure 1).
The first synthesis was reported by Steglich et al. in
2000, starting from tetra-substituted pyrrole by following a
sequence of reactions involving a Rh(II)acetate catalyzed
carbene insertion and an intramolecular Friedel-Crafts acyl-
ation for the construction of the benzo[e]indole-dione nin-
galin C core.2 Two years later, Ruchirawat et al. reported
the second synthesis in which a base catalyzed cyclization
of tetrasubstituted 1,4-naphthoquinone was utilized.3
As a part of our ongoing research program on aryl
hydrazides,4 we have previously reported total syntheses of
ningalin D and G, utilizing [3,3]-sigmatropic rearrangement
reactions of dinaphthyl hydrazides and cyclizations.4b In
this account, we report a new synthesis of ningalin C as an
extension of our investigations on bioactive pyrrole marine
alkaloids. Our retrosynthesis of the titled compound is
delineated in Scheme 1.
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxi-
dation delivered aldehyde 2 in 60% total yields over two
steps. Baeyer–Villiger oxidation, hydrolysis, and air oxidation
gave rise to benzo[e]indole-dione 11 in 37% overall yield.
Efforts to improve the yield were not successful. In fact, a
similar yield was reported for the similar transformation. We
then screened the methods and conditions for the selective
bromination at C4-position. After extensive optimization, we
learned that bromination with HBr in dimethyl sulfoxide
(DMSO) under the conditions reported by Jiao et al.5 were
most effective, providing bromide 12 in 51% yield. Suzuki–
Miyaura reaction with (3,4-dimethoxyphenyl)-boronic acid
(13) provided 1 in 86% yield. BBr3-mediated demethylation
reactions completed the synthesis of ningaln C over nine steps
from the known naphthalene 5 in 4.8% overall yield. The
spectral data of our synthetic ningalin C are consistent with
the literature values.
In summary, we have achieved a total synthesis of ninga-
lin C using [3,3]-sigmatropic rearrangement and cyclization
cascade as key reaction.
Experimental
Unless otherwise stated, reactions were performed under an
argon atmosphere using freshly dried solvents. Tetrahydro-
furan (THF), dichloromethane, toluene, and ethyl ether
were dried by passing through activated alumina columns.
All other commercially obtained reagents were used as
received. All reactions were monitored by thin-layer chro-
matography using EMD/Merck silica gel 60 F254 pre-
coated plates (0.25 mm; Darmstadt, Germany). The TLC
spots were visualized under ultraviolet lamp or using stain-
ing solutions such as ceric ammonium molybdate solution,
p-anisaldehyde solution, ninhydrin solution, or potassium
permanganate solution. Flash column chromatography was
performed with indicated solvents using silica gel
(GS60–40/75) purchased from Fuji Silysia Chemical (Kasu-
gai, Aichi JAPAN). A CEM Discover microwave reaction
system was used for the carbazole synthesis. 1H nuclear
magnetic resonance (NMR) and 13C spectra were recorded
on 400 MHz (Bruker Avance III HD, Billerica, MA, USA)
spectrometer at 400 and 100 MHz, respectively. Chemical
shifts are reported relative to tetramethylsilane (0 ppm) or
It was anticipated that the densely functionalized pyrroli-
dinone system could be synthesized from benzo[e]indole
2
through oxidation and subsequent installation of
3,4-dimethoxyphenyl group. The key benzo[e]indole
3 could be accessed from aryl vinyl hydrazide 4 through a
[3,3]-sigmatropic rearrangement and cyclization casca-
de.4b,4h,4i,4q Further analysis would require aryl bromide
5, styryl bromide 6, and bis-Boc-hydrazine 7.
The synthesis began with the assembly of hydrazide
4 (Scheme 2). The C N coupling reaction between aryl bro-
mide 54b and bis-Boc hydrazine 7 gave aryl hydrazide 8 in
87% yield. The resulting coupling product 8 was then coupled
with vinyl bromide 6 to afford aryl vinyl hydrazide 4 in 98%
yield. Subsequent acid-catalyzed [3,3]-sigmatropic rearrange-
ment and cyclization cascade reaction produced the corre-
sponding benzo[e]indole 3 in 83% yield, when heated with
ZnCl2 in 1,4-dioxane under reflux. Treatment with dimethoxy-
phenethyl iodide 9 in the presence of KOH followed by 2,3-
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KOREAN CHEMICAL SOCIETY
OH HO
OH HO
OH HO
Me
7, CuI, Cs2CO3
1,10-phenanthroline
6, CuI,
Cs2CO3, DMEDA
HO
OH HO
OH
HO
OH
O
Me
MeO
MeO
MeO
MeO
DMF, 80 oC, 87%
THF, 70 oC, 98%
OMe
NBoc
Br
O
NBoc
Br
O
O
H
H
O
NBoc
N
N
N
5
8
7
NBoc
H
O
6
OMe
OH HO
OH
Me
Me
MeO
MeO
OH
HO
OH
MeO
OH
OH
OH
OH
OH
OH
ZnCl2
9, KOH, DMF
MeO
MeO
NBoc
NBoc
NH
I
dioxane, 90 o
83%
C
rt, 78%
MeO
MeO
ningalin B
ningalin C
ningalin D
OMe
OMe
MeO
Figure 1. Structures of ningalin B, C, and D.
4
3
9
Me
CHO
MeO
MeO
MeO
DDQ, AcOH, H2O
H2O2, AcOH
MeO
MeO
MeO
NR
NR
dioxane, rt, 77%
OMe
37%
MeO
MeO
R =
OMe
10
2
O
MeO
MeO
5 O
MeO
MeO
13, Pd(PPh3)4
K3PO4, 1,4-dioxane
Br
HBr (1.2 equiv)
DMSO (1.2 equiv)
4
NR
100 oC, 86%
NR
2
MeO
MeO
DCM, reflux
51%
MeO
MeO
1
O
(HO)2B
13
OH
OMe
O
12
11
OMe
OMe
OMe
O
O
MeO
MeO
HO
HO
OH
OH
OH
BBr3, DCM
NR
N
cyclohexene
-78 oC, 70%
MeO
MeO
HO
HO
O
O
1
ningalin C
Scheme 1. Retrosynthetic analysis of ningalin C.
Scheme 2. Synthesis of ningalin C.
internal chloroform (1H, δ = 7.26, 13C, δ = 77.16) as indi-
cated. Infrared spectra were recorded on an ABB
FTLA2000 FTIR (ABB, Québec, Canada) spectrometer.
High-resolution mass spectra were measured by using ESI-
TOF method at Korean Basic Research Center, O-Chang,
Republic of Korea.
CDCl3) δ 19.7, 28.28, 28.31, 55.8, 81.5, 82.1, 102.9, 106.1,
107.2, 119.3, 122.2, 126.4, 129.3, 133.2, 138.0, 149.2,
149.4, 154.0, 155.51; Fourier-transform infrared spectros-
copy (FT-IR) (CH2Cl2, cm−1) 1714, 2976, 3326; electro-
spray ionization high resolution mass spectrometry (ESI-
HRMS) calcd for C23H32N2NaO6 [M + Na]+ 455.2153,
found 455.2158.
Di-tert-butyl 1-(6,7-dimethoxy-4-methylnaphthalen-2-yl)-
hydrazine-1,2-dicarboxylate (8). A solution of 3-bromo-
6,7-dimethoxy-1-methylnaphthalene 5 (400 mg, 1.42 mmol),
di-tert-butyl hydrazodicarboxylate (7, 662 mg, 2.85 mmol),
CuI (542 mg 2.85 mmol), 1,10-phenonthroline (513 mg,
2.85 mmol), Cs2CO3 (928 mg, 2.85 mmol), in dimethylfor-
mamide (DMF) (3 mL) was stirred under Ar atmosphere in
a sealed tube at 80ꢀC for 24 h. The reaction mixture was
then cooled to room temperature and filtered through a pad
of silica gel with the aid of EtOAc. The reaction mixture
was concentrated under reduced pressure and purified by
flash column chromatography (hexane/EtOAc = 2/1) to give
naphthyl hydrazide 8 as a white solid (535 mg, 87% yield).
1H NMR (400 MHz, CDCl3) δ 1.51 (s, 18H), 2.59 (s, 3H),
3.95 (s, 3H), 3.99 (s, 3H), 6.96 (s, 1H), 7.06 (s, 1H), 7.12 (s,
1H), 7.28 (s, 1H), 7.59 (s, 1H); 13C NMR (100 MHz,
Di-tert-butyl (E)-1-(6,7-dimethoxy-4-methylnaphthalen-
2-yl)-2-(3,4-dimethoxystyryl)hydrazine-1,2-dicarboxylate
(4). A mixture of aryl hydrazide 8 (2.533 g, 5.86 mmol),
(E)-4-(2-bromo-vinyl)-1,2-dimethoxybenzene (6, 2.847 g,
11.7 mmol), CuI (0.223 g, 1.17 mmol), Cs2CO3 (3.816 g,
11.7 mmol), N,N0-dimethylethylenediamine (0.25 mL,
2.34 mmol) in THF (29 mL) was stirred under Ar atmo-
sphere in sealed tube at 70ꢀC overnight. The reaction was
then cooled to room temperature and filtered through a pad
of silica gel with the aid of EtOAc. The reaction mixture
was concentrated under reduced pressure and purified by
flash column chromatography (hexane/EtOAc = 3/1) to
naphthyl styryl hydrazide 4 as a white solid (3.399 g, 98%
1
yield). H NMR (400 MHz, CDCl3) δ 1.48 (s, 9H), 1.54
(s, 9H), 2.63 (s, 3H), 3.85 (s, 3H), 3.89 (s, 3H), 3.98
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(s, 3H), 4.00 (s, 3H), 6.06 (d, 1H, J = 14.4 Hz), 6.79
(d, 1H, J = 8.3 Hz), 6.85 (dd, 1H, J = 8.3, 1.8 Hz), 6.91
(d, 1H, J = 1.8 Hz), 7.09 (s, 1H), 7.15 (s, 1H), 7.37
(s, 1H), 7.67 (d, 1H, J = 14.4 Hz); 13C NMR (100 MHz,
CDCl3) δ 19.9, 28.1, 28.2, 28.3, 55.8, 55.9, 56.0, 82.3,
82.8, 83.3, 102.8, 106.0, 106.4, 107.1, 107.2, 108.1, 109.1,
109.2, 109.6, 111.4, 118.8, 124.4, 125.6, 125.9, 126.2,
129.3, 133.3, 136.6; FT-IR (CH2Cl2, cm−1) 1654, 1722,
3058; ESI-HRMS calcd for C33H42N2NaO8 [M + Na]+
617.2833, found 617.2839.
104.3, 105.0, 109.9, 111.1, 111.4, 112.3, 113.8, 118.3,
119.0, 120.8, 122.4, 123.8, 124.2, 124.6, 127.8, 130.1,
131.3, 132.1, 146.7, 147.90, 147.91, 148.3, 148.7, 149.0;
FT-IR (CH2Cl2, cm−1) 1027, 2832 2938; ESI-HRMS calcd
for C33H35NNaO6 [M + Na]+ 564.2357, found 564.2362.
3-(3,4-Dimethoxyphenethyl)-1-(3,4-dimethoxyphenyl)-
7,8-dimethoxy-3H-benzo[e]indole-5-carbaldehyde
(2).
To a solution of N-alkylated benzo[e]indole 10 (50 mg,
0.09 mmol) dissolved in 1,4-dioxane (0.18 mL) were added
DDQ (74 mg, 0.32 mmol), HOAc (1 drop) and H2O
(1 drop) at room temperature. The reaction mixture was
stirred for 5 min, quenched by adding brine and extracted
with DCM. The combined organic solution was washed
with brine, dried over anhydrous MgSO4 and filtered. The
filtrate was concentrated under reduced pressure and puri-
fied by column chromatography (hexane/EtOAc = 1/1) to
1-(3,4-Dimethoxyphenyl)-7,8-dimethoxy-5-methyl-3H-
benzo[e]indole (3). A mixture of naphthyl styryl hydrazide
4 (1.320 g, 2.22 mmol), ZnCl2 (0.666 g, 4.89 mmol) in
anhydrous 1,4-dioxane (22 mL) was heated at 90ꢀC in a
sealed tube under Ar atmosphere. After 4.5 h, the reaction
mixture was cooled to room temperature, quenched by add-
ing saturated aqueous Na2CO3 and saturated aqueous
NH4Cl, and the resulting mixture was extracted with
dichloromethane (DCM) a few times. The combined
organic solution was dried over anhydrous MgSO4, filtered,
and concentrated under reduced pressure and purified by
column chromatography (CH2Cl2/EtOAc = 50/1) to give
1
give aldehyde 2 as a brown solid (39 mg, 77%). H NMR
(400 MHz, CDCl3) δ 3.15 (t, 2H, J = 6.7 Hz), 3.58 (s,
3H), 3.64 (s, 3H), 3.84 (s, 3H), 3.87 (s, 3H), 3.95 (s, 3H),
4.06 (s, 3H), 4.52 (t, 2H, J = 6.7 Hz), 6.35 (d, 1H,
J = 1.8 Hz), 6.66 (dd, 1H, J = 1.9 Hz, 8.1 Hz), 6.78 (d,
1H, J = 8.2 Hz), 6.97–7.05 (m, 4H), 7.52 (s, 1H), 7.78 (s,
1H), 8.94 (s, 1H), 10.23 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 36.9, 48.9, 55.4, 55.8, 56.0, 56.0, 56.1, 56.2,
103.9, 105.9, 111.2, 111.6, 112.2, 113.7, 119.2, 120.9,
122.1, 122.1, 124.4, 125.1, 125.7, 128.6, 130.7, 131.1,
148.2, 148.4, 148.86, 148.91, 149.1, 193.3; FT-IR
(CH2Cl2, cm−1) 1218, 1664, 2360; ESI-HRMS calcd for
C33H33NNaO7 [M + Na]+ 578.2149, found 578.2155.
1
benzo[e]indole 3 as a yellow solid (0.692 g, 83% yield). H
NMR (400 MHz, CDCl3) δ 2.67 (s, 3H), 3.60 (s, 3H), 3.83
(s, 3H), 3.92 (s, 3H), 3.99 (s, 3H), 6.95 (s, 1H), 6.97 (s,
1H), 7.01 (d, 1H, J = 2.4 Hz), 7.12–7.15 (m, 2H), 7.19 (d,
1H, J = 0.8 Hz), 7.31 (s, 1H), 7.55 (s, 1H), 8.46 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 20.5, 55.4, 55.8, 55.9,
56.1, 104.4, 105.0, 111.1, 111.6, 113.8, 118.3, 119.8,
120.5, 122.5, 123.9, 124.0, 128.3, 130.1, 132.3, 146.6,
148.0, 148.2, 148.6; FT-IR (CH2Cl2, cm−1) 1023, 2360,
3357; ESI-HRMS calcd for C23H23NNaO4 [M + Na]+
400.1519, found 400.1525.
3-(3,4-Dimethoxyphenethyl)-1-(3,4-dimethoxyphenyl)-
3-(3,4-Dimethoxyphenethyl)-1-(3,4-dimethoxyphenyl)-
7,8-dimethoxy-5-methyl-3H-benzo[e]indole (10). To a
stirred solution of benzo[e]indole 3 (0.669 g, 1.77 mmol)
in anhydrous DMF (7 mL) was added solid KOH (1.990 g,
35.5 mmol) at room temperature. The resulting suspension
was stirred at room temperature for 30 min. To this mix-
ture, 4-(2-chloroethyl)-1,2-dimethoxybenzene (9, 2.313 g,
11.5 mmol) was added in portions at room temperature.
The resulting mixture was stirred overnight, quenched with
saturated aqueous NH4Cl, diluted with water and extracted
with EtOAc. The combined organic solution was washed
with brine, dried over anhydrous Na2SO4, and filtered. The
filtrate was concentrated under reduced pressure and puri-
fied by column chromatography (hexane/EtOAc = 3/1) to
give N-alkylated benzo[e]indole 10 as a yellow solid
7,8-dimethoxy-2H-benzo[e]indole-2,5(3H)-dione
(11).
To a flask charged with indole aldehyde 2 (428 mg,
0.77 mmol) and AcOH (4.3 mL) was added 30% H2O2
(1.4 mL) at room temperature. After 5 h, reaction was
quenched with H2O (4.5 mL) and extracted with DCM a
few times. The combined organic solution was washed with
brine, dried over anhydrous MgSO4 and filtered. The filtrate
was concentrated under reduced pressure and purified by
column chromatography (hexane/EtOAc = 1/1) to give 11
as red amorphous solid (159 mg, 37%). 1H NMR
(400 MHz, CDCl3) δ 2.92 (t, 2H, J = 7.6 Hz), 3.55 (s,
3H), 3.85 (s, 3H), 3.86 (s, 3H), 3.87 (t, 2H, J = 1.36 Hz),
3.89 (s, 3H), 3.95 (s, 3H), 3.97 (s, 3H), 5.97 (s 1H), 6.75
(s, 1H), 6.808 (s, 1H), 6.814 (s, 1H), 7.00 (d, 1H,
J = 8.4 Hz), 7.05 (d, 1H, J = 2.0 Hz), 7.17 (dd, 1H,
J = 8.4 Hz, 2.0 Hz), 7.30 (s, 1H), 7.62 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 34.1, 41.7, 56.0, 56.06, 56.07, 56.2,
56.3, 104.3, 108.0, 109.3, 111.3, 111.6, 112.1, 112.8,
121.0, 122.8, 123.2, 123.9, 125.1, 130.3, 130.8, 132.5,
148.1, 149.2, 149.3, 150.5, 150.8, 152.1, 152.4, 170.1,
183.9; FT-IR (CH2Cl2, cm−1) 1143, 1633, 1712; ESI-
HRMS calcd for C32H31NNaO8 [M + Na]+ 580.1942,
found 580.1947.
1
(0.747 g, 78% yield). H NMR (400 MHz, CDCl3) δ 2.73
(s, 3H), 3.10 (t, 2H, J = 7.0 Hz), 3.61 (s, 3H), 3.66 (s, 3H),
3.84 (s, 3H), 3.86 (s, 3H), 3.93 (s, 3H), 4.01 (s, 3H), 4.38
(t, 2H, J = 7.0 Hz), 6.39 (d, 1H, J = 1.9 Hz), 6.69 (dd, 1H,
J = 8.1, 1.9 Hz), 6.75 (s, 1H), 6.78 (d, 1H, J = 8.2 Hz),
6.80 (d, 1H, J = 8.1 Hz), 7.04–7.09 (m, 2H), 7.23 (s, 1H),
7.31 (s, 1H), 7.55 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
20.8, 36.7, 48.5, 55.5, 55.8, 55.96, 55.91, 55.98, 56.1,
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4-Bromo-3-(3,4-dimethoxyphenethyl)-1-(3,4-dimethoxy-
phenyl)-7,8-dimethoxy-2H-benzo[e]indole-2,5(3H)-dione
(12). To a solution of benzo[e]indole-dione 11 (30 mg,
0.06 mmol), DMSO (5 μL, 0.07 mmol) in DCM (2 mL)
was added hydrobromic acid (48%, 7 μL, 0.07 mmol)
under air. The resulting solution was heated under reflux at
60ꢀC for 5 h and cooled down to room temperature. Reac-
tion mixture was washed with brine, dried over anhydrous
MgSO4, filtered, concentrated under reduced pressure and
purified by column chromatography (DCM/EtOAc = 20/1)
room temperature. The organic phase was separated, and
the remaining aqueous phase was saturated with NaCl
(s) and extracted with ethyl acetate (2 × 5 mL). The com-
bined organic solution was washed with brine and dried
over anhydrous Na2SO4. Removal of the solvent in vacuo
gave a red solid, which was purified by preparative thin
layered chromatography (5% methanol in EtOAc) to give
ningalin C as an amorphous red solid (14 mg, 70% yield).
1H NMR (400 MHz, CDCl3) δ 2.38 (t, 2H, J = 7.8 Hz),
3.35–3.60 (m, 2H), 6.16 (dd, 1H, J = 2.0 Hz, 8.1 Hz), 6.38
(d, 1H, J = 2.0 Hz), 6.56 (d, 1H, J = 8.0 Hz), 6.68 (dd,
1H, J = 8.0, 2.0 Hz), 6.81–6.93 (m, 5H), 7.20 (s, 1H), 7.41
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 35.4, 44.2, 113.7,
114.6, 116.2, 116.3, 116.9, 117.1, 117.7, 119.4, 120.9,
121.3, 123.0, 123.5, 124.0, 124.6, 124.7, 125.3, 131.0,
131.5, 135.5, 144.7, 146.0, 146.1, 146.8, 147.1, 148.1,
148.9, 149.4, 151.8, 173.1, 185.8.
1
to give bromide 12 (18 mg, 51%). H NMR (400 MHz,
CDCl3) δ 2.98 (t, 2H, J = 7.8 Hz), 3.50 (s, 3H), 3.83 (s,
3H), 3.85 (s, 3H), 3.89 (s, 3H), 3.94 (s, 3H), 3.97 (s, 3H),
4.42 (t, 2H, J = 7.8 Hz), 6.789 (s, 1H), 6.79 (s, 1H), 6.82
(s, 1H), 6.84 (dd, 1H, J = 1.8 Hz, 8.1 Hz), 6.97 (d, 1H,
J = 1.9 Hz), 7.00 (d, 1H, J = 8.3 Hz), 7.10 (dd, 1H,
J = 8.3, 1.9 Hz), 7.20 (s, 1H), 7.64 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 34.0, 42.8, 55.9, 55.92, 56.0, 56.2,
56.4, 103.9, 108.0, 110.0, 111.5, 111.5, 112.3, 112.6,
121.2, 122.5, 123.0, 123.5, 124.1, 130.2, 130.4, 134.7,
148.0, 149.0, 149.4, 149.5, 150.6, 150.9, 152.4, 170.6,
177.8; FT-IR (CH2Cl2, cm−1) 1073, 1588, 1713; ESI-
HRMS calcd for C32H30BrNNaO8 [M + Na]+ 658.1047,
found 658.1052.
Acknowledgments. This work was supported by the
grants from the National Research Foundation of Korea
(2012M3A7B4049657).
Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
Permethyl Ningalin C (1). To a sealed tube bromide 12
(36 mg, 0.2 mmol), (PPh3)4Pd (7.7 mg, 0.007 mmol),
K3PO4 (169 mg, 0.8 mmol), and 1,4-dioxane (1.3 mL) were
added under Ar atmosphere. The sealed tube was capped
and heated at 100ꢀC overnight. The reaction was then cooled
to room temperature and filtered through a pad of silica gel
with the aid of EtOAc. The reaction mixture was concen-
trated under reduced pressure and purified by flash column
chromatography (100% DCM gives DCM/MeOH = 100/1)
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to give permethyl ningalin C (1, 40 mg, 86%). H NMR
(400 MHz, CDCl3) δ 2.54 (s, 2H, J = 8.0 Hz), 3.48–3.64
(m, 2H), 3.56 (s, 3H), 3.78 (s, 3H), 3.82 (s, 3H), 3.93 (s,
3H), 3.94 (s, 3H), 3.96 (s, 3H), 3.970 (s, 3H) 3.972 (s, 3H),
6.31 (d, 1H, J = 1.6 Hz), 6.42 (dd, 1H, J = 8.0, 2.0 Hz),
6.70 (d, 1H, J = 8.4 Hz), 6.99 (s, 1H), 7.00 (s, 1H), 7.04 (d,
1H, J = 8.0 Hz), 7.07 (d, 1H, J = 2.0 Hz), 7.19 (dd, 1H,
J = 8.4, 2.0 Hz), 7.64 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 34.9, 43.2, 55.7, 55.8, 55.9, 55.9, 56.0, 56.1, 107.8, 109.4,
110.9, 111.2, 111.3, 111.7, 112.7, 114.2, 119.0, 120.8,
122.9, 123.1, 123.7, 123.8, 124.5, 125.0, 130.3, 130.5,
134.3, 147.2, 147.6, 148.6, 148.8, 149.3, 149.5, 150.2,
150.7, 152.1, 170.9, 183.7.
Ningalin C. To a flask charged with permethyl ningalin C
(1, 24 mg, 0.035 mmol), anhydrous CH2Cl2 (3.7 mL) was
added and the solution was cooled to −78ꢀC. To the solu-
tion, BBr3 dissolved in CH2Cl2 (1.0 M, 0.46 mL,
0.46 mmol) was added and the resulting mixture was
warmed to room temperature and stirred overnight. The
solution was then cooled with an ice bath before adding
water (2.5 mL) and the mixture was stirred for 30 min at
Bull. Korean Chem. Soc. 2018
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
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